The Danish Trial of Weight Loss to Reduce Atrial Fibrillation Progression
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 480
- 试验地点
- 2
- 主要终点
- Hierarchical composite outcome capturing AF progression and AF burden, inte-grating clinical events assessed by blinded adjudication and objective measures of AF burden, assessed by 14-day continuous ECG monitoring
研究概览
简要总结
Obesity is an important risk factor for the development and progression of atrial fibrillation. Sustainable weight loss likely reduces the burden of atrial fibrillation, which has yet to be proven in adequately sized randomised trials.
In a national, multicentre randomised trial we will test, whether a sustainable weight loss of more than 10% reduces atrial fibrillation progression and burden in patients with symptomatic paroxysmal or early persistent atrial fibrillation and a body mass index ≥27 kg/m2. A total of 480 patients will be randomised in a 1:1 fashion to either a comprehensive weight loss programme of behavioural support, meal replacement and/or pharmacotherapy with a glucagon-like peptide-1 receptor agonist on top of standard care aiming at more than 10% weight loss or standard care alone. Standard care will include guideline-directed anticoagulant therapy for stroke prevention, rate and/or rhythm control treatment, and management of risk factors and underlying cardiovascular conditions. Patients in the standard care group will receive information on weight management, but no active treatment for weight loss. Patients will be enrolled during a period of two and a half years and will be followed for one year with an equal number of study visits in both study arms. All patients will receive a 14-day continuous electrocardiographic monitoring at baseline, four, eight, and 12 months.
The study endpoints will be assessed after a 4-months blanking period from month four to 12 to allow for weight loss. The primary endpoint will be a hierarchical composite of atrial fibrillation progression, symptom burden, and treatment escalation. Secondary endpoints will be a change in weight, total atrial fibrillation burden, quality of life, and metabolic and cardiovascular biomarkers from baseline to 12 months. Safety endpoints will be adverse events related to treatment with glucagon-like peptide-1 receptor agonists and weight loss. Endpoint adjudication will be blinded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic paroxysmal* or persistent** AF
- •Sinus rhythm at inclusion (Visit 1)
- •BMI ≥27 kg/m2
- •Age>18 years
- •At least one 12-lead ECG or other single- or multiple-lead ECG device (e.g. Holter monitor-ing or ECG-providing wearables) documented episode during 6 months prior to inclusion
- •* Paroxysmal AF in this trial is defined as at least 2 episodes, either self-terminating or cardioverted within 7 days, during 6 months prior to in-clusion
- •**Persistent AF in this study is defined as the following:
- •Duration of an AF episode >7 days and < 6 months
- •Total documented AF history < 5 years
排除标准
- •Atrial flutter as the primary arrhythmia. (Patients with previous or isolated episodes of atrial flutter may be included, provided that AF is the dominant arrhythmia and the primary target of clinical management)
- •Implanted electronic device (pacemaker/ICD/ICM)
- •Type 1 diabetes or Type 2 diabetes on insulin treatment
- •Severe heart failure (LVEF <40%)
- •Inability to sign informed consent
- •Severe kidney disease (eGFR<30)
- •History of catheter ablation for AF
- •Scheduled to receive catheter ablation for AF during the study period (next 1 year)
- •Incretin-based therapy (GLP-1 receptor agonists or DPP-IV inhibitors) within 30 days prior to randomization (visit 1)
- •Scheduled for bariatric surgery during the study period
- •Hypertrophic cardiomyopathy, ARVC/D, non-compaction or amyloidosis
- •Chronic or previous acute pancreatitis
- •Current participation in any other clinical intervention trial that may result in changes to med-ical management during the study period
- •Women of childbearing potential who are not on an acceptable form of contraception
- •Pregnant or breastfeeding women
- •Personal or family history of medullary thyroid carcinoma (MTC)
- •History of MEN2 (Multiple Endocrine Neoplasia type 2)
研究组 & 干预措施
Intervention
Structured weight loss program including behavioral support and optional meal re-placement or pharmacotherapy with Glucagon-like peptide-1 receptor agonists (GLP1-RA), aiming for >10% weight loss on top of standard care.
干预措施: Structured weight loss program including behavioral support and optional meal re-placement or pharmacotherapy with Glucagon-like peptide-1 receptor agonists (GLP1-RA) (Other)
Control
Standard care, including cardiovascular risk factor management, with visit frequency and follow-up similar to the intervention group.
干预措施: Standard Care (in control arm) (Other)
结局指标
主要结局
Hierarchical composite outcome capturing AF progression and AF burden, inte-grating clinical events assessed by blinded adjudication and objective measures of AF burden, assessed by 14-day continuous ECG monitoring
时间窗: From 4 months to 12 months after enrollment
The hierarchical components of the primary outcome are: 1. Unplanned contact to a cardiology department or emergency department visit with a primary diagnosis of AF 2. Unplanned hospital visit for heart failure 3. High AF burden defined as: AF burden ≥10% (i.e., ≥33.8 hours of cumulative AF) during any of the 14-day ECG monitoring periods at 4, 8, or 12 months 4. Moderate AF burden defined as: AF burden ≥5% (i.e., ≥16.8 hours of cumulative AF) during any of the 14-day ECG monitoring periods at 4, 8, or 12 months 5. Planned cardioversion (electrical or pharmacological), including pill-in-the-pocket therapy using Class Ic antiarrhythmic agents (e.g. flecainide)
次要结局
未报告次要终点
研究者
Axel Brandes
Professor, M.D.
Esbjerg Hospital - University Hospital of Southern Denmark